OBJECTIVETo assess the prognostic value of CD20(+) tumor-infiltrating lymphocytes (TILs) in early-stage breast cancer.

METHODSParaffin sections were collected from 130 cases of stage I-III breast cancer undergoing surgery between January, 2000 and December, 2002 in our hospital. Immunohistochemistry was used to analyze mesenchymal CD20(+) TILs infiltration in the tumor and evaluate its association with the density of CD4(+) and CD8(+) TILs. The association of CD20(+) TILs was evaluated with the histopathologic features, overall survival (OS), distant disease-free survival (DDFS), and disease-free survival (DFS) of the patients.

RESULTSAggregations of CD20(+) lymphocytes were observed in 37.69% (49/130) of the cases. CD3(+) T cells were found to aggregate around CD20(+) B cell aggregations to form lymphoid follicle-like structures. The aggregations of CD20(+) TILs were positively correlated with the densities of mesenchymal CD8+ and CD4(+) TILs. Overall, CD20(+) TIL aggregations were not significantly correlated with the outcomes of the patients, but multivariate COX regressions suggested that CD20(+) TIL aggregations were positively correlated with DDFS (HR=0.251, 95% CI=0.071-0.894, P=0.033) and OS (HR=0.325, 95% CI=0.103-1.028, P=0.056) in hormone receptor-negative patients but not in the positive patients. Further analysis suggested that post-operative adjuvant endocrine therapy significantly improved the OS of patients positive for hormone receptors without CD20(+) TIL aggregations (P=0.001).

CONCLUSIONThe long-term therapeutic effects of adjuvant endocrine therapy are correlated with CD20(+) TIL aggregations to affect prognostic value of CD20(+) TIL aggregations in early-stage breast cancer patients.

Antigens, CD20 ; metabolism ; B-Lymphocytes ; cytology ; Breast Neoplasms ; immunology ; pathology ; Disease-Free Survival ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating ; cytology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Survival Rate

Occupational silicosis (hereinafter referred to as "silicosis") exhibited individual differences in disease susceptibility, with genetic factors playing a crucial role in its onset and progression. Cytokines, such as interleukin (IL)-1RA +2018T>C locus, tumor necrosis factor-α -308G>A and -238G>A locus, transforming growth factor (TGF)-β1 +915G>C locus, were related to the development of silicosis. However, relationship between IL-17F +7488A>G and TGF-β1 -509T>C locus with silicosis had shown inconsistent results across different studies. Regulatory proteins such as matrix metalloproteinase (MMP)-2 -735C>T locus, MMP-9 rs3918242 locus, heat shock protein (HSP) 70-1+190G>C locus, carboxypeptidase M rs12812500 locus, family sequence similarity gene 13A (FAM13A) rs2609255 locus, and desmoplakin rs2076304 locus were also related to the development of silicosis. The A allele of the non-coding RNA miRNA-4508 rs6576457 increased the risk of developing silicosis-related pulmonary fibrosis in dust-exposed workers. The polymorphism in the long non-coding RNA ADGRG3 rs1814521 was related to silicosis susceptibility. Additionally, six circular RNAs of small nucleolar RNA host gene 14 rs17115143 sequence might be potential biomarkers of silicosis. Human leukocyte antigen-DR (HLA-DR) genes demonstrated a dual role in both risk and protection against silicosis, while angiotensin I-converting enzyme (ACE) gene polymorphisms likely affected silicosis development by modulating serum ACE activity. However, the mechanisms by which certain genetic variations affected susceptibility to silicosis remain unclear. Prospective studies with large-scale samples combining genetics, epidemiology, bioinformatics, and biofunctional studies are needed to promote the development of biomarkers for silicosis susceptibility and disease course, and clinical therapies.

OBJECTIVETo explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis.

METHODSParaffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4⁺ and CD8⁺ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients.

RESULTSAPRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4⁺ cells (P<0.001) and CD8⁺ cells (P<0.001). In hormone receptor negative patients (ER- and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). CONCLUSIONSl APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Breast Neoplasms ; diagnosis ; metabolism ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Transformation, Neoplastic ; Cytoplasm ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Retrospective Studies ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; metabolism

Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.

Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis. Methods Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4+ and CD8+ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+cells (P<0.001) and CD8+cells (P<0.001). In hormone receptor negative patients (ER-and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis. Methods Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4+ and CD8+ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+cells (P<0.001) and CD8+cells (P<0.001). In hormone receptor negative patients (ER-and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Objective:To explore the clinical efficacy of venovenous extracorporeal membrane oxygenation(V-V ECMO)in patients with severe acute respiratory distress syndrome(ARDS)caused by Pneumocystis pneumonitis(PJP)after kidney transplantation(KT).Methods:Cal data of 9 KT recipients on V-V ECMO were retrospectively analyzed. Timing of V-V ECMO support, complications during treatment and V-V ECMO performance were summarized.Results:All 9 patients with confirmed PJP adopted V-V ECMO with oxygenation index of 25~92 prior to V-V ECMO and average time from admission to initiating V-V ECMO was 5.56(1~17)days. Except for one death from hemorrhagic shock due to abdominal hemorrhage, the remainders were successfully weaned. Another recipient died from sepsis after weaning and there were 7 survivors. V-V ECMO support time was 215.5 h among 8 successfully weaned recipients. Among 7 survivors, 1 had premorbid deterioration of graft function and no fatal complications occurred.Conclusions:V-V ECMO is an effective treatment for severe ARDS caused by P. pneumoniae post-KT. And its early application is recommended for reducing complications and improving patient prognosis.

Objective By comparing biomechanical properties of two-screw rod and three-screw rod for fixing pelvic fracture, the difference in mechanical effects of different screw rod fixation positions in pelvic minimally invasive surgery was studied.Methods The mechanical models of pelvis fixed by two-screw rod and three-screw rod were established, and biomechanical characteristics of the pelvis during standing on both legs, during single-legged standing on healthy side or affected side, as well as in sitting posture were compared and analyzed by finite element simulation, and the fixation effect of three-screw rod was verified by clinical experiments.Results Both fixation methods could restore mechanical transmission of the pelvis. But for three-screw rod fixation, the stress on both sides of the pelvis was more balanced, and the displacement of the whole body and fracture surface was also lower during single-legged standing.Conclusions The three-screw rod fixation has an excellent effect in stability, which is more beneficial for fracture recovery.

Objective:To investigate the effects of ultrasound-guided thoracic paravertebral block on the changes of analgesic efficacy and inflammatory response in patients with multiple rib fractures.Methods:A retrospective case-control study was performed in 48 patients with multiple rib fractures admitted to 909th Hospital of Joint Logistics Support Force from July 2016 to December 2018. There were 30 males and 18 females, with the age range of 18-69 years[(41.1±10.4)years]. The number of fractured ribs was 3-9 (5.7±1.9). All patients were stabilized with the memory alloy embracing fixator. Thoracic paravertebral block group received ultrasound-guided thoracic paravertebral block and intravenous analgesia group received patient controlled intravenous analgesia, with 24 patients in each group. The visual analogue scale (VAS) was observed and recorded in the resting/cough state before induction of anesthesia(T1), and 1 h (T2), 6 h (T3), 24 h (T4) and 48 h (T5) after surgery. Blood samples were taken simultaneously from the vein for determination of plasma neutrophil elastase (NE), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations by ELISA method.Results:In the resting state, there was no significant difference between two groups in VAS at T1 ( P>0.05); the VAS in two groups at T2-T5 decreased significantly compared with T1 ( P<0.01); the VAS at T2-T4 in thoracic paravertebral block group [(3.4±0.7)points, (3.2±0.8)points, (3.1±0.7)points] was significantly lower than that in intravenous analgesia group [(4.8±0.9)points, (4.4±0.7)points, (3.9±0.8)points]( P<0.01 ). In the cough state, there was no significant difference between two groups in VAS at T1 ( P>0.05); the VAS at T2-T5 in intravenous analgesia group was all higher than 6 points[(7.7±1.0)points, (7.6±1.3)points, (7.4±1.2)points, (7.1±0.9)point], and was significantly higher than those in thoracic paravertebral block group [(3.6±0.7)points, (3.3±0.7)points, (3.2±0.6)points, (2.9±0.7)points] ( P<0.01). There was no significant difference between two groups in plasma levels of NE, TNF-α and IL-6 at T1 ( P>0.05). Their levels at T2 in two groups were significantly increased, but were decreased at T5 compared with those at T1 ( P<0.01). The plasma levels of NE, TNF-α and IL-6 were significantly lower in thoracic paravertebral block group at T2-T5 [NE: (65.5±19.0)ng/ml, (42.5±12.5)ng/ml, (26.3±9.3)ng/ml, (20.9±7.9)ng/ml; TNF-α: (8.7±1.9)pg/ml, (6.0±1.3)pg/ml, (3.9±0.9)pg/ml, (2.8±0.8)pg/ml; IL-6: (11.5±3.6)pg/ml, (6.7±1.8)pg/ml, (3.6±1.0)pg/ml, (2.5±0.7)pg/ml] than those in intravenous analgesia group[NE: (76.7±18.2)ng/ml, (51.4±15.1)ng/ml, (35.5±10.0)ng/ml, (28.6±9.0)ng/ml; TNF-α: (10.0±2.1)pg/ml, (6.8±1.5)pg/ml, (4.7±1.1)pg/ml, (3.6±1.0)pg/ml; IL-6: (16.2±4.2)pg/ml, (8.7±2.1)pg/ml, (5.7±1.2)pg/ml, (3.5±0.7)pg/ml] ( P<0.05 or 0.01). Conclusion:Compared with intravenous analgesia, ultrasound-guided thoracic paravertebral block can provide better analgesic effect, reduce the plasma levels of inflammatory cytokines that result from trauma and surgery, and down-regulate inflammatory response.

Objective:To understand the genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike protein variations during different epidemic periods in Wuxi City.Methods:Nucleic acid was extracted from the nasopharyngeal swab samples of six local cases of coronavirus disease 2019 (COVID-19) (from January to February, 2020) and 13 imported cases of COVID-19 (from March to September, 2021) in Wuxi City, and the whole genome was amplified to construct the sequencing library. The second-generation sequencer was used for sequencing. The CLC Genomics Workbench (21 version) software was used to analyze the offline data with NC_045512.2 as the reference strain, and MEGA 7.0 software was used to construct the phylogenetic tree.Identification of type was conducted by Nextstrain typing method and phylogenetic assignment of named global outbreak lineages (Pangolin) typing method.Results:There were five subtypes in Nextstrain and seven subtypes in Pangolin of the nineteen patients with COVID-19. Compared with NC_045512.2, the median nucleotide mutation sites were 29 (range 0 to 42) and amino acid mutation sites were 20 (range 0 to 34). The six local and 13 imported cases had no common nucleotide mutation sites and were in different evolutionary branches. The sequences of the six local cases were highly homologous with the reference strain sequences (NC_045512.2) at the early stage of the pandemic, and the evolutionary distance was close to that of the reference strain. The 13 imported cases were obviously divided into three evolutionary branches (Alpha, Beta, Delta variant).The four Beta variants shared eight amino acid mutation sites in spike protein, and the two Alpha variants shared eight amino acid mutation sites in spike protein, and the seven Delta variants shared five amino acid mutation sites in spike protein.Conclusions:New mutations of SARS-CoV-2 are constantly emerging during the epidemic. The increase of the nucleotide sites number may result in the change of spike protein amino acid. Therefore, the whole-genome sequencing analysis plays an important role in the accurate tracing of epidemic origin and adjustment of prevention and control measures.